Social drinking (the consumption of alcohol without becoming intoxicated) is a social norm in many cultures and has long been considered an acceptable practice which allows people to socialize more freely and easily together. Drinking is relaxing for many people, and drinking before and during parties, at bars or restaurants, with meals and with family and friends are all acts considered to be within the realm of social drinking, when alcohol consumption is maintained so that intoxication is not reached.
More excessive or serious forms of drinking, often chronic, may be potentially harmful to the drinker and to others affected by the drinker. For example, drinking with the intent to get drunk or intoxicated, drinking and driving while under the influence of alcohol, loss of psychomotor coordination and speech, blackouts, vomiting, alcohol poisoning and associated deaths are considered among the harmful symptoms and effects of drinking that falls outside the scope of social drinking. It would be desirable to avoid these and other effects or consequences of excessive alcohol consumption.
Alcohol abuse, moreover, is a common problem in the general population all over the world. Alcohol abuse and alcoholism are responsible for a wide variety of medical problems, which are considered part of the new-age epidemics, among them the most recognized being alcohol-induced liver disease, primary and secondary malnutrition, and neuron damage, often leading to death.
The pharmaco-therapeutic aspect of alcoholism includes the use of drugs, with different actions and objectives. Metadoxine is a pyridoxine-pyrrolidone carboxylate (also known as pyridoxol L,2-pyrrolidon-5 carboxylate or pyridoxine 5-oxo-2-pyrrolidon-carboxylate) with significant alcohol scavenging properties which has been used to treat acute alcohol intoxication, poisoning, and certain acute alcohol syndromes (reviewed in Addolorato et al., Int. J. Immunopathol. Pharmacal. (2003) 16:207-214). Long term data show that metadoxine is safe for use by humans.
Metadoxine is capable of accelerating the elimination of alcohol from the blood and tissues, helping restore the functional structure of the liver and relieve neuro-psychological disorders associated with chronic alcohol intoxication and associated syndromes. In animal studies, metadoxine increased plasma clearance and urinary excretion of ethanol, inhibited the increased production of fatty acid esters in the liver during chronic alcohol intake, reduced oxidative stress and prevented glutathione depletion in hepatic tissues (Antonelli et al., Pharmacol. Res. Commun. (1984) 16:189-197). In the brain, metadoxine increased the level of GABA and acetylcholine in the frontoparietal cortex of guinea pigs.
Metadoxine is an ion-pair between pyrrolidone carboxylate (PCA) and pyridoxine (vitamin B6) with the two compounds linked in a single product by salification. The pairing with PCA synergistically increases the pharmacological activity of pyridoxine (see, e.g., U.S. Pat. No. 4,313,952). Metadoxine is freely soluble in water and in gastric fluid. Oral absorption of the drug is fast with high bioavailability (60-80%). The half life of metadoxine in human serum is short (40-60 minutes) without appreciable differences between oral and intravenous administration (Addolorato et al., supra; Lu Yuan et al., Chin. Med. J. 2007 120(2) 160-168).
Metadoxine is marketed in several countries as a prescription drug in the form of 500 mg tablets and 300 mg injections. Tablets contain 500 mg of metadoxine, microcrystalline cellulose and magnesium stearate. Ampoules contain 300 mg of metadoxine, sodium metabisulfite, EDTA sodium, methyl-p-hydroxybenzoate and water.
Maximal levels of ethanol appear in the blood stream 30-60 minutes after drinking. Due to the fast absorption of ethanol, stomach wash is ineffective against ethanol overdose. Because ethanol is miscible in water, it will be targeted to water-rich tissues, such as the brain, where it will cause the familiar symptoms. An average drink increases blood ethanol level to about 20 mg/dl, which can typically be metabolized and cleared in about one hour. Up-regulation of alcohol-dehydrogenase (ADH) in heavy drinkers may increase the ethanol clearance to about 30 mg/dl per hour.
There is thus a need for methods and compositions that are capable of quickly reducing alcohol levels and providing quick restoration of sobriety following alcohol consumption in any type of drinking, or that reduce or prevent symptoms of alcohol consumption, particularly in subjects that have not reached intoxication levels or who do not exhibit symptoms of chronic alcoholic related syndromes. It would be desirable, for example, to have a treatment which could be administered during or shortly after social drinking of any amount of alcohol that would enable the drinker to quickly become sober enough to legally drive. There is also a need for better treatment and prevention of acute and chronic alcohol intoxications and related diseases, such as alcoholism.